Title

Author

Document Type

Dissertation

Date of Degree

Summer 2015

Degree Name

PhD (Doctor of Philosophy)

Degree In

Epidemiology

First Advisor

Robert B. Wallace

Abstract

Dementia is a major public health problem worldwide. Emerging research indicates that clinical infections and PTSD could be important risk factors for dementia. However, evidence for infections and the risk of dementia primarily examines central nervous system (CNS) infections. Extant epidemiological evidence for systemic bacterial infections and the risk for dementia is limited while that for PTSD and the risk for dementia did not account for psychotropic medications commonly used in management of PTSD and could affect cognitive function. The purpose of this study was to 1) review the evidence for CNS infections as possible causes of Alzheimer’s disease (AD) dementia, and 2) using nationwide Veterans Health Administration databases, conduct original retrospective cohort analyses in nationally representative samples of U.S. veterans aged 56 years and older to determine the associations between systemic bacterial infections, PTSD, and psychotropic PTSD medication use with the risk for developing dementia.

Review of the research pertaining to an infectious AD etiology hypothesis including the various mechanisms through which different clinical and subclinical infections could cause or promote the progression of AD, and the concordance between putative infectious agents and the epidemiology of AD showed evidence linking AD to an infectious cause to be largely inconclusive; however, the amount of evidence suggestive of an association is too substantial to ignore.

Analysis of the associations between PTSD and psychotropic PTSD medication use with the risk for dementia showed a significant association between PTSD and the risk for dementia (HR=1.35; 95%CI=1.27-1.43) after adjustment for demographic characteristics, medical and psychiatric comorbidity, and health care utilization. Analysis of the impact of psychotropic PTSD medications including selective serotonin reuptake inhibitors (SSRI), serotonin-norepinephrine reuptake inhibitors (SNRI), benzodiazepines (BZA), novel antidepressants (NA) and atypical antipsychotics (AA) on the association between PTSD and the risk for dementia showed significant interactions between PTSD and use of SSRIs (p

These findings indicate; 1) evidence for an infectious AD etiology hypothesis in inconclusive, 2) both severe (e.g. sepsis), and less severe (e.g. cellulitis) systemic bacterial infections are collectively and independently associated with an increased risk of dementia among older U.S. veterans hence prevention of systemic bacterial infections could positively influence the risk for dementia among older adults, and 3) PTSD and psychotropic medication use are associated with an increased risk for dementia among U.S. veterans.

Further epidemiologic, clinical, and basic science research is required to elucidate the mechanisms and the associations between infections and the risk for dementia and to determine if the independent and effect modifying impacts of psychotropic PTSD medication use on the risk for dementia are related to differences in PTSD severity, other psychiatric comorbidity, or whether psychotropic PTSD medication use is an independent risk factor for dementia.